scholarly journals Analysis of Plasmodium falciparum Pfcrt and Pfmdr1 genes in parasite isolates from asymptomatic individuals in Southeast Nigeria 11 years after withdrawal of chloroquine

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Moses N. Ikegbunam ◽  
Charles N. Nkonganyi ◽  
Bolaji N. Thomas ◽  
Charles O. Esimone ◽  
Thirumalaisamy P. Velavan ◽  
...  

Abstract Background A reversal of chloroquine (CQ) resistance following a period of withdrawal has raised the possibility of its re-introduction. This study evaluated the current prevalence of Pfcrt and Pfmdr1 alleles in Plasmodium falciparum isolates, 11 years after CQ withdrawal in Southeast Nigeria. Methods Filter-paper blood samples were collected from 725 non-febrile individuals, comprising 250 children (≤ 12 years), 250 pregnant women and 225 other adults, between October 2014 and February 2015 in Nnewi town, Southeast Nigeria. Nested PCR followed by direct sequencing was employed for the genotyping of Pfcrt and Pfmdr1 genes. Results A total of 103 parasites-positive samples were recovered, comprising of 48 (19.20%) among children, 20 (20.00%) among pregnant women and 35 (15.50%) among other adults cohort. The frequency of the mutant genotype of Pfcrt 76T, 75E and 74I was 94.50% each. Parasite isolates from children had a frequency of 100% for mutant alleles in all Pfcrt codons while isolates from pregnant women and other adults had a frequency of 91% each in all codons. Haplotype distribution of pfcrt gene were 5.45, 0.00 and 76.37% for CVMNK, SVMNT and CVIET, respectively. For Pfmdr1 gene, the frequency of 86Y, 184F and 1246Y mutant alleles were 8.54, 29.27 and 3.66%, respectively. Amongst the Pfmdr1 haplotypes analysed, NFD had the highest frequency of 24.4%, followed by YFD at 6.10%. NYF and NYY occurred the least (1.20%). Conclusion The high level of Pfcrt mutations is suggestive of a sustained CQ pressure on P. falciparum isolates in the study area, despite the change of first line treatment from CQ to artemisinin combination therapy for 11 years. A new strategy to ensure the complete withdrawal of CQ from the country is recommended.

2010 ◽  
Vol 78 (5) ◽  
pp. 1963-1978 ◽  
Author(s):  
Mirja Hommel ◽  
Salenna R. Elliott ◽  
Viju Soma ◽  
Greg Kelly ◽  
Freya J. I. Fowkes ◽  
...  

ABSTRACTPregnant women are infected by specific variants ofPlasmodium falciparumthat adhere and accumulate in the placenta. Using serological and molecular approaches, we assessed the global antigenic diversity of surface antigens expressed by placenta-binding isolates to better understand immunity to malaria in pregnancy and evolution of polymorphisms and to inform vaccine development. We found that placenta-binding isolates originating from all major regions where malaria occurs were commonly recognized by antibodies in different populations of pregnant women. There was substantial antigenic overlap and sharing of epitopes between isolates, including isolates from distant geographic locations, suggesting that there are limitations to antigenic diversity; however, differences between populations and isolates were also seen. Many women had cross-reactive antibodies and/or a broad repertoire of antibodies to different isolates. Studying VAR2CSA as the major antigen expressed by placenta-binding isolates, we identified antibody epitopes encoded by variable sequence blocks in the DBL3 domain. Analysis of globalvar2csaDBL3 sequences demonstrated that there was extensive sharing of variable blocks between Africa, Asia, Papua New Guinea, and Latin America, which likely contributes to the high level of antigenic overlap between different isolates. However, there was also evidence of geographic clustering of sequences and differences in VAR2CSA sequences between populations. The results indicate that there is limited antigenic diversity in placenta-binding isolates and may explain why immunity to malaria in pregnancy can be achieved after exposure during one pregnancy. Inclusion of a limited number of variants in a candidate vaccine may be sufficient for broad population coverage, but geographic considerations may also have to be included in vaccine design.


2017 ◽  
Vol 7 (4) ◽  
pp. 247-260 ◽  
Author(s):  
Irène Pegha-Moukandja ◽  
Roméo-Karl Imboumy-Limoukou ◽  
Nina Tchitoula-Makaya ◽  
Augustin-Ghislain Mouinga-Ondeme ◽  
Jean Claude Biteghe-Bi-Essone ◽  
...  

2015 ◽  
Vol 59 (8) ◽  
pp. 4631-4643 ◽  
Author(s):  
Suwanna Chaorattanakawee ◽  
David L. Saunders ◽  
Darapiseth Sea ◽  
Nitima Chanarat ◽  
Kritsanai Yingyuen ◽  
...  

ABSTRACTCambodia's first-line artemisinin combination therapy, dihydroartemisinin-piperaquine (DHA-PPQ), is no longer sufficiently curative against multidrug-resistantPlasmodium falciparummalaria at some Thai-Cambodian border regions. We report recent (2008 to 2013) drug resistance trends in 753 isolates from northern, western, and southern Cambodia by surveying forex vivodrug susceptibility and molecular drug resistance markers to guide the selection of an effective alternative to DHA-PPQ. Over the last 3 study years, PPQ susceptibility declined dramatically (geomean 50% inhibitory concentration [IC50] increased from 12.8 to 29.6 nM), while mefloquine (MQ) sensitivity doubled (67.1 to 26 nM) in northern Cambodia. These changes in drug susceptibility were significantly associated with a decreased prevalence ofP. falciparummultidrug resistance 1 gene (Pfmdr1) multiple copy isolates and coincided with the timing of replacing artesunate-mefloquine (AS-MQ) with DHA-PPQ as the first-line therapy. Widespread chloroquine resistance was suggested by all isolates being of theP. falciparumchloroquine resistance transporter gene CVIET haplotype. Nearly all isolates collected from the most recent years hadP. falciparumkelch13mutations, indicative of artemisinin resistance.Ex vivobioassay measurements of antimalarial activity in plasma indicated 20% of patients recently took antimalarials, and their plasma had activity (median of 49.8 nM DHA equivalents) suggestive of substantialin vivodrug pressure. Overall, our findings suggest DHA-PPQ failures are associated with emerging PPQ resistance in a background of artemisinin resistance. The observed connection between drug policy changes and significant reduction in PPQ susceptibility with mitigation of MQ resistance supports reintroduction of AS-MQ, in conjunction with monitoring of theP. falciparummdr1copy number, as a stop-gap measure in areas of DHA-PPQ failure.


2015 ◽  
Vol 60 (3) ◽  
pp. 1274-1282 ◽  
Author(s):  
Myaing M. Nyunt ◽  
Vy K. Nguyen ◽  
Richard Kajubi ◽  
Liusheng Huang ◽  
Joshua Ssebuliba ◽  
...  

Artemether-lumefantrine is a first-line regimen for the treatment of uncomplicated malaria during the second and third trimesters of pregnancy. Previous studies have reported changes in the pharmacokinetics and clinical outcomes following treatment with artemether-lumefantrine in pregnant women compared to nonpregnant adults; however, the results are inconclusive. We conducted a study in rural Uganda to compare the pharmacokinetics of artemether-lumefantrine and the treatment responses between 30 pregnant women and 30 nonpregnant adults with uncomplicatedPlasmodium falciparummalaria. All participants were uninfected with HIV, treated with a six-dose regimen of artemether-lumefantrine, and monitored clinically for 42 days. The pharmacokinetics of artemether, its metabolite dihydroartemisinin, and lumefantrine were evaluated for 21 days following treatment. We found no significant differences in the overall pharmacokinetics of artemether, dihydroartemisinin, or lumefantrine in a direct comparison of pregnant women to nonpregnant adults, except for a statistically significant but small difference in the terminal elimination half-lives of both dihydroartemisinin and lumefantrine. There were seven PCR-confirmed reinfections (5 pregnant and 2 nonpregnant participants). The observation of a shorter terminal half-life for lumefantrine may have contributed to a higher frequency of reinfection or a shorter posttreatment prophylactic period in pregnant women than in nonpregnant adults. While the comparable overall pharmacokinetic exposure is reassuring, studies are needed to further optimize antimalarial efficacy in pregnant women, particularly in high-transmission settings and because of emerging drug resistance. (This study is registered at ClinicalTrials.gov under registration no. NCT01717885.)


2018 ◽  
Vol 62 (1) ◽  
pp. 111-121
Author(s):  
Raúl Hileno ◽  
Antonio García-de-Alcaraz ◽  
Bernat Buscà ◽  
Cristòfol Salas ◽  
Oleguer Camerino

Abstract In volleyball, attack coverage is one of the play actions most neglected in coaching and research. The purpose of this study was to find out which attack coverage systems are used by high-level men’s teams in different game situations and the characteristics of the most effective systems. We analysed 15 matches from the 2010 Men’s Pan-American Volleyball Cup, with a total of 1,415 coverage actions. Chi-square tests for independence, adjusted residuals analysis and calculations of standardised mean difference were performed. The results show that high-level men’s volleyball uses many coverage systems other than the traditional 3-2-0 and 2-3-0. At this level of play, the most frequent systems were 1-3-1 and 1-2-2, which occurred significantly often at the culmination of a third-tempo attack at the wing. The most effective systems consisted of three coverage lines, with fewer than five players covering the spiker and at least one player in the first coverage line, in both the attack and counterattack phases. Given the large number of coverage systems identified in different game situations, we recommend flexible, loosely structured training in these systems, based on a set of guiding principles that all players on a team must internalise for the specific position they are playing. Regarding the systems’ efficacy, the main watchword is that on each coverage line there should always be at least one player, but the first line should not be exposed.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Armel Djènontin ◽  
Aziz Bouraima ◽  
Christophe Soares ◽  
Seun Egbinola ◽  
Gilles Cottrell

Abstract Objective In the framework of EVALMOUS study aiming to assess the use and effectiveness of mosquito nets by pregnant women and other members of their household in a lagoon area in southern Benin, the behaviour of pregnant women relative to the time they go to bed using the net were recorded. Malaria vectors biting rhythm, Plasmodium falciparum infection and insecticide resistance genes in malaria vectors were also determined. Results Overall, 3848 females of Anopheles gambiae s. l were collected and 280 pregnant women responded to the survey. Almost all Anopheles gambiae s. l. tested were Anopheles coluzzi Coetzee and Wilkerson 2013 (Diptera: Culicidae). The CSP index in malaria vector was 1.85% and the allelic frequency of kdr gene was 74.4%. Around 90% of bites and Plasmodium falciparum Welch, 1897 (Haemosporida: Plasmodiidae) transmission occurred between 10 p.m. and 6 a.m., which coincides with the period when more than 80% of pregnant women were under bednet. Despite a slight early evening and early morning biting activity of malaria vectors in the study area, the good use of nets might remain a useful protection tool against mosquito biting and malaria transmission.


2018 ◽  
pp. 118-121
Author(s):  
L.M. Vygivska ◽  
◽  
I.A. Usevych ◽  
I.V. Maidannyk ◽  
V.F. Oleshko ◽  
...  

The article represents the results of a prospective clinical and paraclinical examination of women with a history of infertility, pregnancy in which occurred as a result of the assisted reproductive technologies application. The objective: was to study the dynamics of pregnancy features of the psycho - emotional state and the concentration of stress-associated hormones in the serum of pregnant women after the application of assisted reproductive technologies in order to improve the tactics of antenatal care and prevention of obstetric and perinatal complications. Materials and methods. The main group consisted of 80 pregnant women with endocrine infertility, in which pregnancy occurred as a result of therapeutic cycles of ART, control – 50 first-pregnant women with spontaneous fertilization, taken in an arbitrary order of clinical, statistical and laboratory and instrumental studies. In pregnant women of the study groups, in order to determine the psycho emotional state in the screening mode, a clinical interview was conducted by filling out questionnaires that contained the Spilberger test questions in modification of Y.L. Hanina and «Test of relationof pregnant» by the method of I.V. Dobryakova. In the dynamics of pregnancy, the concentration of prolactin (PRL) and cortisol (K) was determined by the enzyme immunoassay on the Reader-MSR-1000 apparatus using test systems manufactured by Hema-Medicament (Russia). Results. Pregnant women with infertility in past history were characterized by a state of chronic stress. According to the results of the Spielberger test in modification Y .L. Hanina every second pregnant of main group had a high level of reactive and every fourth personal anxiety. Almost 90.0% of pregnant women after art are characterized by the presence of pathological PKGD, among which an alarming and depressive type was registered in every sixth and twelfth pregnant woman, respectively. The obtained data are confirmed by the results of the study of the level of K and PRL. For women with a history of infertility and pregnancy, which is the result of therapeutic cycles of ART, inherent in increasing concentrations of stress-associated hormones – cortisol and prolactin, which is one of the reasons for the complicated course of pregnancy and requires reasonable pathogenetic correction. Conclusion. For women who are pregnant as a result of the use of therapeutic cycles of art characterized by a high level of personal and reactive anxiety and PKGD, which confirm the presence of neuropsychiatric and afferent disorders. Increasing the concentration of stress-associated hormones is one of the causes of complicated pregnancy and requires a reasonable pathogenetic correction. Key words: pregnancy, infertility, assisted reproductive technologies, psychological status, cortisol, prolactin.


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